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To Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-drug Conjugate, GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or in Combination With Bortezomib Plus Dexamethasone (Arm B) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM 6)

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ClinicalTrials.gov Identifier: NCT03544281
Recruitment Status : Recruiting
First Posted : June 1, 2018
Last Update Posted : May 19, 2021
Sponsor:
Collaborator:
Iqvia Pty Ltd
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE April 30, 2018
First Posted Date  ICMJE June 1, 2018
Last Update Posted Date May 19, 2021
Actual Study Start Date  ICMJE September 20, 2018
Estimated Primary Completion Date April 28, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 9, 2020)
  • Number of participants with DLTs, Part 1, Treatment A [ Time Frame: Up to 28 days ]
    The number of participants with DLTs will be reported.
  • Number of participants with DLTs, Part 1, Treatment B [ Time Frame: Up to 21 days ]
    The number of participants with DLTs will be reported.
  • Number of participants with AEs and serious adverse events (SAEs), Part 1 [ Time Frame: Up to 4.5 years ]
    AEs and SAEs will be collected.
  • Number of participants with electrocardiogram (ECG) parameters of potential clinical importance (PCI), Part 1 [ Time Frame: Up to 4.5 years ]
    Twelve-lead ECGs, will be performed, with the participant at designated time points, using an ECG machine, after 5 minutes of rest. The number of participants with PCI values, will be reported.
  • Number of participants with abnormal hematology parameters, Part 1 [ Time Frame: Up to 4.5 years ]
    Blood sample will be collected for the assessment of hematology parameters.
  • Number of participants with abnormal clinical chemistry parameters, Part 1 [ Time Frame: Up to 4.5 years ]
    Blood sample will be collected for the assessment of hematology parameters.
  • Number of participants with abnormal urinalysis parameters, Part 1 [ Time Frame: Up to 4.5 years ]
    Urine samples will be collected for the assessment of urinalysis parameters.
  • Number of participants with vital signs of PCI, Part 1 [ Time Frame: Up to 4.5 years ]
    Number of participants with abnormal vital signs will be assessed.
  • Number of participants with AEs and SAEs in Part 2 [ Time Frame: Up to 4.5 years ]
    AEs and SAEs will be collected.
  • Overall Response Rate (ORR) as defined by the International Myeloma Working Group (IMWG) Uniform Response Criteria for multiple myeloma (MM), Part 2 [ Time Frame: Up to 4.5 years ]
    ORR defined as percentage (%) of participants achieving >=Partial Response (PR) as defined by the IMWG Uniform Response Criteria for MM.
Original Primary Outcome Measures  ICMJE
 (submitted: May 23, 2018)
  • Number of subjects with AE's and serious adverse events (SAEs),Part 1 [ Time Frame: up to 4.5 years ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect and other situations which involve medical or scientific judgment, and is associated with liver injury and impaired liver function The number of subject experiencing SAE and AEs during Part 1 of the study will be reported.
  • Number of subjects with electrocardiogram (ECG) parameters of potential clinical importance (PCI), Part 1 [ Time Frame: up to 4.5 years ]
    Twelve-lead ECGs, will be performed, with the subject at designated time points, using an ECG machine, after 5 minutes of rest. The number of subjects with PCI values, will be reported.
  • Number of subjects with abnormal hematology parameters, Part 1 [ Time Frame: up to 4.5 years ]
    Blood samples will be collected to measure platelets, white blood cell (WBC count), red blood cell (RBC) count, reticulocyte count, hemoglobin, hematocrit, RBC indices, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), basophils, eosinophils, lymphocytes, monocytes and neutrophils.
  • Number of subjects with abnormal clinical chemistry parameters, Part 1 [ Time Frame: up to 4.5 years ]
    Blood samples will be collected to measure blood urea nitrogen (BUN), creatinine, fasting glucose, sodium, magnesium, potassium, chloride, Total carbon dioxide (CO2), phosphorous, calcium, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, creatinine kinase (CK), total and direct bilirubin, uric acid, albumin, total protein, lactate dehydrogenase (LDH).
  • Number of subjects with abnormal urinalysis parameters, Part 1 [ Time Frame: up to 4.5 years ]
    Urine samples will be collected to measure specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick method at specified time points.
  • Number of subjects with vital signs of PCI, Part 1 [ Time Frame: up to 4.5 years ]
    The number of subjects with vital signs of PCI, for systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature and heart rate. Vitals will be measured after specific time points after at least 5 minutes of rest.
  • Percentage of subject's with dose-limiting toxicities (DLTs), Part 1 [ Time Frame: up to 4.5 years ]
    The percentage of subject's with DLT's will be reported.
  • Percentage of subjects with Complete Response (CR) Rate, Part 2 [ Time Frame: up to 4.5 years ]
    CR rate defined as the percentage of subjects with a confirmed CR or better (i.e., CR and stringent CR [sCR]), according to the International Myeloma Working Group (IMWG) Response Criteria.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 9, 2020)
  • Maximum plasma concentration (Cmax) for belantamab mafodotin, Part 1 and 2, Treatment A [ Time Frame: Cycle 1: Predose, at end of infusion, 2 hours, 24 hours after end of infusion, Day 4, Day 8 to Day 15, and Day 29 (cycle duration=28 days) ]
    Serial blood samples will be collected for pharmacokinetic (PK) analysis.
  • Area under the concentration time curve (AUC) for belantamab mafodotin, Part 1 and 2, Treatment A [ Time Frame: Cycle 1: Predose, at end of infusion, 2 hours, 24 hours after end of infusion, Day 4, Day 8 to Day 15, and Day 29 (cycle duration=28 days) ]
    Serial blood samples will be collected for PK analysis.
  • Time to maximum plasma concentration (Tmax) for belantamab mafodotin, Part 1 and 2, Treatment A [ Time Frame: Cycle 1: Predose, at end of infusion, 2 hours, 24 hours after end of infusion, Day 4, Day 8 to Day 15, and Day 29 (cycle duration=28 days) ]
    Serial blood samples will be collected for PK analysis.
  • Serum half-life (t1/2) for belantamab mafodotin, Part 1 and 2, Treatment A [ Time Frame: Cycle 1: Predose, at end of infusion, 2 hours, 24 hours after end of infusion, Day 4, Day 8 to Day 15, and Day 29 (cycle duration=28 days) ]
    Serial blood samples will be collected for PK analysis.
  • Cmax for belantamab mafodotin, Part 1 and 2, Treatment B [ Time Frame: Cycle 1: Predose, at end of infusion, 2 hours, 24 hours after end of infusion, Day 4, Day 11, and Day 22 (cycle duration=21 days) ]
    Serial blood samples will be collected for PK analysis.
  • AUC for belantamab mafodotin, Part 1 and 2, Treatment B [ Time Frame: Cycle 1: Predose, at end of infusion, 2 hours, 24 hours after end of infusion, Day 4, Day 11, and Day 22 (cycle duration=21 days) ]
    Serial blood samples will be collected for PK analysis.
  • Tmax for belantamab mafodotin, Part 1 and 2, Treatment B [ Time Frame: Cycle 1: Predose, at end of infusion, 2 hours, 24 hours after end of infusion, Day 4, Day 11, and Day 22 (cycle duration=21 days) ]
    Serial blood samples will be collected for PK analysis.
  • t1/2 for belantamab mafodotin, Part 1 and 2, Treatment B [ Time Frame: Cycle 1: Predose, at end of infusion, 2 hours, 24 hours after end of infusion, Day 4, Day 11, and Day 22 (cycle duration=21 days) ]
    Serial blood samples will be collected for PK analysis.
  • Cmax for Lenalidomide, Part 1 and 2, Treatment A [ Time Frame: Pre-dose, and 0.5, 1, 2, 4, and 24 hours post dose on Day 1 of Cycle 1 (cycle duration=28 days) ]
    Serial blood samples will be collected for PK analysis.
  • AUC for Lenalidomide, Part 1 and 2, Treatment A [ Time Frame: Pre-dose, and 0.5, 1, 2, 4, and 24 hours post dose on Day 1 of Cycle 1 (cycle duration=28 days) ]
    Serial blood samples will be collected for PK analysis.
  • Tmax for Lenalidomide, Part 1 and 2, Treatment A [ Time Frame: Pre-dose, and 0.5, 1, 2, 4, and 24 hours post dose on Day 1 of Cycle 1 (cycle duration=28 days) ]
    Serial blood samples will be collected for PK analysis.
  • t1/2 for Lenalidomide, Part 1 and 2, Treatment A [ Time Frame: Pre-dose, and 0.5, 1, 2, 4, and 24 hours post dose on Day 1 of Cycle 1 (cycle duration=28 days) ]
    Serial blood samples will be collected for PK analysis.
  • Cmax for Bortezomib, Part 1 and 2, Treatment B [ Time Frame: Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (cycle duration=21 days) ]
    Serial blood samples will be collected for PK analysis.
  • AUC for Bortezomib, Part 1 and 2, Treatment B [ Time Frame: Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (cycle duration=21 days) ]
    Serial blood samples will be collected for PK analysis.
  • Tmax for Bortezomib, Part 1 and 2, Treatment B [ Time Frame: Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (cycle duration=21 days) ]
    Serial blood samples will be collected for PK analysis.
  • t1/2 for Bortezomib, Part 1 and 2, Treatment B [ Time Frame: Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (cycle duration=21 days) ]
    Serial blood samples will be collected for PK analysis.
  • Number of participants with anti-drug antibodies (ADAs) against belantamab mafodotin, Part 1 and 2, Treatment A [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (cycle duration=28 days) ]
    The number of participants with ADAs will be assessed.
  • Number of participants with ADAs, against belantamab mafodotin, Part 1 and 2, treatment B [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (Cycle duration= 21 days) ]
    The number of participants with ADAs will be assessed.
  • Change from Baseline in symptoms and impacts as measured by Ocular Surface Disease Index (OSDI), Part 1 and 2 [ Time Frame: Baseline and up to 4.5 years ]
    The OSDI, is a 12-item questionnaire designed to assess both the frequency of dry eye symptoms and their impact on vision-related functioning. The OSDI has demonstrated good reliability, validity, sensitivity, and specificity, and can be used as a complement to other clinical and subjective measures of dry eye disease by providing a quantifiable assessment of dry eye symptom frequency and the impact of these symptoms on vision-related functioning. The OSDI will be measured at every 4-weeks, for Treatment A and every 3-weeks, for Treatment B.
  • Change from Baseline in symptoms and impacts as measured by the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25), Part 1 and 2 [ Time Frame: Baseline and up to 4.5 years ]
    The NEI-VFQ-25, consists of a base set of 25 vision-targeted questions representing, 11 vision-related constructs, plus an additional single-item, general health rating question. These include, a global vision rating (1 item); difficulty with near vision activities (3 items); difficulty with distance vision activities (3 items); limitations in social functioning due to vision (2 items); role limitations due to vision (2 items); dependency on others due to vision (3 items); mental health symptoms due to vision (4 items); driving difficulties (3 items); limitations with peripheral vision (1 item), limitations with color vision (1 item); and Ocular pain (2 items). Scores will be measured, every 4-weeks, for Treatment and every 3-weeks, for Treatment B.
  • Change from Baseline in symptoms and impacts as measured by Patient-Reported Outcome Version of the Common Term Criteria for Adverse Events (PRO-CTCAE), Part 1 and 2 [ Time Frame: Baseline and up to 4.5 years ]
    The PRO-CTCAE is a participant-reported outcome measure developed to evaluate symptomatic toxicity in participants on cancer clinical trials. The PRO-CTCAE includes an item library of 124 items representing 80 symptomatic toxicities drawn from the CTCAE.
  • Number of participants with AEs and SAEs, Part 2 [ Time Frame: Up to 4.5 years ]
    AEs and SAEs will be collected.
  • Number of participants with AEs of special interest (AESI), Part 1 and 2 [ Time Frame: Up to 4.5 years ]
    The AEs of special interest will be collected.
  • Number of participants with ophthalmic findings on ophthalmic exam, Part 1 and 2 [ Time Frame: Up to 4.5 years ]
    The ophthalmic examinations will be done, by an ophthalmologist (or optometrist), to assess participants who develop corneal events, during the study.
  • Change from Baseline in health related quality of life (HRQoL) as measured by European Organization for Research and Treatment of Cancer Quality of life Questionnaire 30-item core module (EORTC QLQ-C30), Part 1 and 2 [ Time Frame: Baseline and Up to 4.5 years ]
    EORTC QLQ-C30, is a 30-item questionnaire containing both single- and multi-item measures. These include five functional scales (Physical, Role, Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and Nausea/Vomiting), a Global Health Status/QoL scale, and six single items (Constipation, Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). Scores for each scale and single-item measure. A high score for functional scales and for Global Health Status/QoL, represent better functioning ability or HRQoL, whereas a high score for symptom scales and single items represents significant symptomatology.
  • Change from Baseline in HRQoL as measured by EORTC, 20-Item Multiple Myeloma Module (QLQ-MY20), Part 1 and 2 [ Time Frame: Baseline and Up to 4.5 years ]
    QLQ-MY20, module comprises 20 questions that address four myeloma-specific HRQoL domains: Disease Symptoms, Side Effects of Treatment (DSSE), Future Perspective, and Body Image (FPBI). Three of four QLQ-MY20 domains, are multi-item scales: Disease Symptoms (bone aches or pain, back pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity); Side effects of treatment (drowsiness, thirst, feeling ill, dry mouth, hair loss, upset by hair loss, tingling hands or feet, restlessness/agitation, acid indigestion/heartburn, and burning or sore eyes); and Future perspective (worry about death and health in future, and thinking about illness). The Body Image scale is single-item scale that addresses physical attractiveness. A high score for DSSE, represents a high level of symptomatology or problems, whereas high score for FPBI, represents better outcomes.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2018)
  • Maximum plasma concentration (Cmax) for Lenalidomide, Part 1, Treatment A [ Time Frame: At pre-dose, and 0.5, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days) ]
    Serial blood samples of approximately 4 milliliter (mL) each will be collected for analysis.
  • Area under the concentration time curve (AUC) for Lenalidomide, Part 1, Treatment A [ Time Frame: At pre-dose, and 0.5, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • Time to maximum plasma concentration (Tmax) for Lenalidomide, Part 1, Treatment A [ Time Frame: At pre-dose, and 0.5, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • Half life (t1/2) for Lenalidomide, Part 1, Treatment A [ Time Frame: At pre-dose, and 0.5, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • Cmax for Lenalidomide, Part 2, Treatment A [ Time Frame: At pre-dose, and 0.5 hour, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • AUC for Lenalidomide, Part 2, Treatment A [ Time Frame: At pre-dose, and 0.5 hour, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • Tmax for Lenalidomide, Part 2, Treatment A [ Time Frame: At pre-dose, and 0.5 hour, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • t1/2 for Lenalidomide, Part 2, Treatment A [ Time Frame: At pre-dose, and 0.5 hour, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • Number of subjects with anti-drug antibodies (ADAs) against GSK2857916, Part 1, Treatment A [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (Each cycle is of 28 days) ]
    The number of subjects with ADAs will be reported. All ADA samples will be collected prior to each infusion (at Cycle 1, 2, 3, 6, 9, 12) on the dosing days in Part 1, at the same time as the pre-dose GSK2857916, pharmacokinetic (PK) samples.
  • Number of subjects with ADAS, against GSK2857916, Part 1 treatment B [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (Each cycle is of 21 days) ]
    The number of subjects with ADAs will be reported. All ADA samples will be collected prior to each infusion (at Cycle 1, 2, 3, 6, 9, 12) on the dosing days in Part 1, at the same time as the pre-dose GSK2857916, PK samples.
  • Change from Baseline in symptoms and impacts as measured by Ocular Surface Disease Index (OSDI), Part 1 [ Time Frame: Baseline and up to 4.5 years ]
    The OSDI, is a 12-item questionnaire designed to assess both the frequency of dry eye symptoms and their impact on vision-related functioning. The OSDI has demonstrated good reliability, validity, sensitivity, and specificity, and can be used as a complement to other clinical and subjective measures of dry eye disease by providing a quantifiable assessment of dry eye symptom frequency and the impact of these symptoms on vision-related functioning. Each of the 12 questions is assessed using a 5-point scale (where according to the severity of the case: 0=None of the time, 1=. Some of the time, 2=.Half of the time, 3=.most of the time and 4 all of the time). The scores will be summed and converted to a 0-100 point score, where 0 is no symptoms and 100 is severe symptoms. The scores will be measured at every 4-weeks, for Treatment A and every 3-weeks, for Treatment B.
  • Change from Baseline in symptoms and impacts as measured by the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25), Part 1 [ Time Frame: Baseline and up to 4.5 years ]
    The NEI-VFQ-25, consists of a base set of 25 vision-targeted questions representing, 11 vision-related constructs, plus an additional single-item, general health rating question. These include, a global vision rating (1 item); difficulty with near vision activities (3 items); difficulty with distance vision activities (3 items); limitations in social functioning due to vision (2 items); role limitations due to vision (2 items); dependency on others due to vision (3 items); mental health symptoms due to vision (4 items); driving difficulties (3 items); limitations with peripheral vision (1 item), limitations with color vision (1 item); and Ocular pain (2 items). Each item will be scored on 0 to 100 scale, and will be calculated, by measuring average for all items. The possible total score range for NEI-VFQ-25 will be from 0 (worst possible outcome) to 100 (best possible outcome). Scores will be measured, every 4-weeks, for Treatm
  • Change from Baseline in symptoms and impacts as measured by Patient-Reported Outcome Version of the Common Term Criteria for Adverse Events (PRO-CTCAE), Part 1 [ Time Frame: Baseline and up to 4.5 years ]
    The PRO-CTCAE is a subject-reported outcome measure developed to evaluate symptomatic toxicity in subjects on cancer clinical trials. The PRO-CTCAE includes an item library of 124 items representing 80 symptomatic toxicities drawn from the CTCAE.
  • Duration of Response (DoR), Part 2 [ Time Frame: up to 4.5 years ]
    DOR, defined as: the time from first documented evidence of PR or better; the time when PD is documented per IMWG; or death due to PD occurs among subjects who achieve an overall response, i.e. confirmed partial response (PR) or better.
  • Time to Response (TTR), Part 2 [ Time Frame: up to 4.5 years ]
    TTR, defined as: the time between the date of first dose and the first documented evidence of response (PR or better).
  • Time to Best Response (TTBR), Part 2 [ Time Frame: up to 4.5 years ]
    TTBR, defined as: the time between the date of first dose and the best documented evidence of response (PR or better).
  • Number of subjects with Progression-free Survival (PFS), Part 2, Treatment A [ Time Frame: Every 4 weeks up to 4.5 years ]
    PFS defined as: the time from first dose until the earliest date of PD per IMWG, or death due to any cause.
  • Time to Disease Progression (TTP), Part 2 [ Time Frame: up to 4.5 years ]
    TTP is defined as, the time from first dose until the earliest date of PD per IMWG, or death due to PD.
  • Overall Survival (OS), Part 2, Treatment A [ Time Frame: Every 4 weeks up to 4.5 years ]
    OS defined as the time from first dose until the date of death due to any cause.
  • Percentage of subjects achieving Minimal residual disease (MRD) negativity, Part 2, Treatment A [ Time Frame: Every 4 weeks up to 4.5 years ]
    MRD negativity defined as the percentage of subjects who are MRD negative.
  • Number of subjects with AE's and SAE's, Part 2 [ Time Frame: up to 4.5 years ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect and other situations which involve medical or scientific judgment, and is associated with liver injury and impaired liver function The number of subject experiencing SAE and AEs during, Part 2 of the study will be reported.
  • Number of subjects with AE's of special interest (AESI), Part 2 [ Time Frame: up to 4.5 years ]
    The AE's of special interest, for GSK2857916 are corneal events, thrombocytopenia and infusion related reactions. The severity of other AESI will be graded utilizing the National Cancer Institute- Common Toxicity Criteria for Adverse Events.
  • Number of subjects with ECG of PCI, Part 2 [ Time Frame: up to 4.5 years ]
    Twelve-lead ECGs will be performed with the subject at designated time-points, using an ECG machine, after 5 minutes of rest. The number of subjects with PCI values, will be reported.
  • Number of subjects with abnormal hematology parameters, Part 2 [ Time Frame: up to 4.5 years ]
    Blood samples will be collected to measure platelets, WBC count, RBC count, reticulocyte count, hemoglobin, hematocrit, red blood cell indices, MCV, MCH, MCHC, basophils, eosinophils, lymphocytes, monocytes and neutrophils.
  • Number of subjects with abnormal clinical chemistry parameters, Part 2 [ Time Frame: up to 4.5 years ]
    Blood samples will be collected to measure BUN, creatinine, fasting glucose, sodium, magnesium, potassium, chloride, Total CO2, phosphorous, calcium, AST, ALT, GGT, alkaline phosphatase, CK, total and direct bilirubin, uric acid, albumin, total protein, and LDH.
  • Number of subjects with abnormal urinalysis parameters, Part 2 [ Time Frame: Up to 4.5 years ]
    Urine samples will be collected to measure specific gravity, pH, glucose, protein, blood and ketones by dipstick method at specified time points.
  • Number of subjects with vital signs of PCI, Part 2 [ Time Frame: up to 4.5 years ]
    The number of subjects with vital signs of PCI, for SBP, DBP, temperature and heart rate, will be reported. The ECG will be measured at specified time points.
  • Number of subjects with ophthalmic findings on ophthalmic exam, Part 2 [ Time Frame: up to 4.5 years ]
    The ophthalmic examinations will be done, by an ophthalmologist (or optometrist), to assess subjects who develop corneal toxicity, during the study.
  • Number of subjects with ADAS, against GSK2857916, Part 2 Treatment A [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (Each cycle is of 28 days) ]
    The number of subjects with ADAs will be reported. All ADA samples will be collected prior to each infusion (at Cycle 1, 2, 3, 6, 9, and Cycle 12) on the dosing days in Part 2 at the same time as the pre-dose GSK2857916 PK samples.
  • Number of subjects with ADAS, against GSK2857916, Part 2, Treatment B [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (Each cycle is of 21 days) ]
    The number of subjects with ADAs will be reported. All ADA samples will be collected prior to each infusion (at Cycle 1, 2, 3, 6, 9, and Cycle 12) on the dosing days in Part 2 at the same time as the pre-dose GSK2857916 PK samples.
  • Change from Baseline in symptoms and impacts as measured by OSDI, Part 2 [ Time Frame: Baseline and up to 4.5 years ]
    The ocular surface disease index (OSDI), is a 12-item questionnaire designed to assess both the frequency of dry eye symptoms and their impact on vision-related functioning. The OSDI has demonstrated good reliability, validity, sensitivity, and specificity, and can be used as a complement to other clinical and subjective measures of dry eye disease by providing a quantifiable assessment of dry eye symptom frequency and the impact of these symptoms on vision-related functioning. Each of the 12 questions is assessed using a 5-point scale (where according to the severity of the case: 0=None of the time, 1=. Some of the time, 2=.Half of the time, 3=.most of the time and 4 all of the time). The scores will be summed and converted to a 0-100 point score, where 0 is no symptoms and 100 is most symptoms. The scores will be measured at every 4-weeks, for Treatment A and every 3-weeks, for Treatment B.
  • Change from Baseline in symptoms and impacts as measured by NEI-VFQ-25, Part 2 [ Time Frame: Baseline and up to 4.5 years ]
    The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) consists of a base set of 25 vision-targeted questions representing, 11 vision-related constructs, plus an additional single-item, general health rating question. These include, a global vision rating (1 item); difficulty with near vision activities (3 items); difficulty with distance vision activities (3 items); limitations in social functioning due to vision (2 items); role limitations due to vision (2 items); dependency on others due to vision (3 items); mental health symptoms due to vision (4 items); driving difficulties (3 items); limitations with peripheral vision (1 item), limitations with color vision (1 item); and Ocular pain (2 items). Each item will be scored on 0 to 100 scale, where the scores will be calculated, by measuring the average for all items. The possible total score range for the NEI-VFQ-25 will be from 0 (worst possible outcome) to 100 (best possible outcome).
  • Change from Baseline in symptoms and impacts as measured by PRO-CTCAE, Part 2 [ Time Frame: Baseline and up to 4.5 years ]
    The Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events is a subject-reported outcome measure developed to evaluate symptomatic toxicity in subjects on cancer clinical trials. The PRO-CTCAE includes an item library of 124 items representing 80 symptomatic toxicities drawn from the CTCAE.
  • Number of subjects with AE leading to discontinuation or dose reduction/delay, Part 2 [ Time Frame: Up to 4.5 years ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The number of subject's with AE leading to discontinuation or delay for study treatment will be reported.
  • Cmax for GSK2857916, Part 1, Treatment A [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • AUC for GSK2857916, Part 1, Treatment A [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • Tmax for GSK2857916, Part 1, Treatment A [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • t1/2 for GSK2857916, Part 1, Treatment A [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • Cmax for GSK2857916, Part 2, Treatment A [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • AUC for GSK2857916, Part 2, Treatment A [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • Tmax for GSK2857916, Part 2, Treatment A [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • t1/2 for GSK2857916, Part 2, Treatment A [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • Cmax for GSK2857916, Part 1, Treatment B [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • AUC for GSK2857916, Part 1, Treatment B [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • Tmax for GSK2857916, Part 1, Treatment B [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • t1/2 for GSK2857916, Part 1, Treatment B [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • Cmax for GSK2857916, Part 2, Treatment B [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • AUC for GSK2857916, Part 2, Treatment B [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • Tmax for GSK2857916, Part 2, Treatment B [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • t1/2 for GSK2857916, Part 2, Treatment B [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • Plasma concentration of GSK2857916, Part 1, Treatment A [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • Plasma concentration of GSK2857916, Part 1, Treatment B [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • Plasma concentration of GSK2857916, Part 2, Treatment A [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis.
  • Plasma concentration of GSK2857916, Part 2, Treatment B [ Time Frame: Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • Cmax for Bortezomib, Part 1, Treatment B [ Time Frame: Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • AUC for Bortezomib, Part 1, Treatment B [ Time Frame: Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • Tmax for Bortezomib, Part 1, Treatment B [ Time Frame: Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • t1/2 for Bortezomib, Part 1, Treatment B [ Time Frame: Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • Cmax for Bortezomib, Part 2, Treatment B [ Time Frame: Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • AUC for Bortezomib, Part 2, Treatment B [ Time Frame: Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • Tmax for Bortezomib, Part 2, Treatment B [ Time Frame: Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • t1/2 for Bortezomib, Part 2, Treatment B [ Time Frame: Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days) ]
    Serial blood samples of approximately 4 mL each will be collected for analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
  • Percentage Of Subjects With Overall Response Rate (ORR), Part 2 [ Time Frame: Up to 4.5 years ]
    ORR is defined as the percentage of subjects with a confirmed PR or better (i.e., PR, very good partial response [VGPR], CR and sCR), according to the IMWG Response Criteria.
  • Number of subjects with PFS, Part 2, Treatment B [ Time Frame: Every 3 weeks up to 4.5 years ]
    PFS defined as: the time from first dose until the earliest date of PD per IMWG, or death due to any cause.
  • OS, Part 2, Treatment B [ Time Frame: Every 3 weeks up to 4.5 years ]
    OS defined as the time from first dose until the date of death due to any cause.
  • Percentage of subjects achieving MRD negativity, Part 2, Treatment B [ Time Frame: Every 3 weeks up to 4.5 years ]
    MRD negativity defined as the percentage of subjects who are MRD negative.
  • Change from Baseline in health related quality of life (HRQoL) as measured by European Organization for Research and Treatment of Cancer Quality of life Questionnaire 30-item core module (EORTC QLQ-C30), Part 2 [ Time Frame: Baseline and Up to 4.5 years ]
    EORTC QLQ-C30, is a 30-item questionnaire containing both single- and multi-item measures. These include five functional scales (Physical, Role, Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and Nausea/Vomiting), a Global Health Status/QoL scale, and six single items (Constipation, Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). Scores for each scale and single-item measure, will be averaged and transformed linearly to a score ranging from 0-100. A high score for functional scales and for Global Health Status/QoL, represent better functioning ability or HRQoL, whereas a high score for symptom scales and single items represents significant symptomatology.
  • Change from Baseline in HRQoL as measured by EORTC, 20-Item Multiple Myeloma Module (QLQ-MY20), Part 2 [ Time Frame: Baseline and Up to 4.5 years ]
    QLQ-MY20, module comprises 20 questions that address four myeloma-specific HRQoL domains: Disease Symptoms, Side Effects of Treatment (DSSE), Future Perspective, and Body Image(FPBI). Three of four QLQ-MY20 domains, are multi-item scales: Disease Symptoms (bone aches or pain, back pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity); Side effects of treatment (drowsiness, thirst, feeling ill, dry mouth, hair loss, upset by hair loss, tingling hands or feet, restlessness/agitation, acid indigestion/heartburn, and burning or sore eyes); and Future perspective (worry about death and health in future, and thinking about illness). The Body Image scale is single-item scale that addresses physical attractiveness. QLQ-MY20 domain scores will be averaged and transformed linearly to score ranging from 0-100. A high score for DSSE, represents a high level of symptomatology or problems, whereas high score for FPBI, represents better outcomes.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE To Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-drug Conjugate, GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or in Combination With Bortezomib Plus Dexamethasone (Arm B) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)
Official Title  ICMJE A Phase I/II, Open-label, Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-Drug Conjugate GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or Bortezomib Plus Dexamethasone (Arm B) in Participants With Relapsed / Refractory Multiple Myeloma - DREAMM-6
Brief Summary

This study will evaluate the safety and tolerability profile of belantamab mafodotin when administered in combination with approved regimens of either Lenalidomide Plus Dexamethasone [Len/Dex (Arm A)] or Bortezomib Plus Dexamethasone [Bor/Dex (Arm B)] in participants with RRMM, i.e., those who have relapsed or who are refractory to at least 1 line of approved therapy. Part 1 of the study will be a dose escalation phase to evaluate the safety and tolerability of up to 3 dose levels and up to 2 dosing schedules of belantamab mafodotin in combination with the two standard of care (SoC) regimens. Part 2 will further evaluate the safety and preliminary clinical activity of belantamab mafodotin at selected dose levels and dosing schedules in combination with Len/Dex or Bor/Dex.

A total of 152 evaluable participants will be enrolled in the study with up to 27 in Part 1 and up to 125 in Part 2. Participants receiving treatment Arm A, may continue combination treatment until the occurrence of progressive disease (PD), intolerable adverse events (AEs ), consent withdrawal, death or end of study. The participants receiving treatment Arm B, may continue combination treatment for a total of up to 8 cycles. After 8 cycles of combination therapy, the participants will continue treatment with belantamab mafodotin, as a monotherapy until the occurrence of PD, intolerable AEs, consent withdrawal, death or end of study.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

This is a 2-part study. Part 1 of the study will be a dose escalation phase to evaluate the safety and tolerability of up to 3 dose levels and up to 2 dosing schedules of belantamab mafodotin in combination with two SoC regimens (Arm A - belantamab mafodotin with Len/Dex and Arm B - belantamab mafodotin with Bor/Dex) For Arm A (belantamab mafodotin with Len/Dex), Part 2 of the study will further evaluate the safety and preliminary clinical activity of up to 2 dose levels and up to 3 dosing schedules of belantamab mafodotin with Len/Dex .

For Arm B (belantamab mafodotin with Bor/Dex), Part 2 of the study will further evaluate the safety and preliminary clinical activity of up to 3 dose levels and up to 4 dosing schedules of belantamab mafodotin with Bor/Dex.

Masking: None (Open Label)
Masking Description:
This is an open-label study; therefore, no blinding of treatment identity will be done for both treatments.
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Belantamab mafodotin
    Selected doses of belantamab mafodotin will be administered as an infusion.
  • Drug: Lenalidomide
    Lenalidomide will be administered as 25 or 10 mg,orally, with belantamab mafodotin and dexamethasone.
  • Drug: Dexamethasone
    Dexamethasone will be administered as 20 or 40 mg, orally with belantamab mafodotin.
  • Drug: Bortezomib
    Bortezomib will be administered as 1.3 mg/m^2, as SC or IV, with belantamab mafodotin and dexamethasone.
Study Arms  ICMJE
  • Experimental: Arm A: Belantamab mafodotin+lenalidomide +dexamethasone

    Participants will receive SINGLE full dose of belantamab mafodotin as 2.5 mg/kg and 1.9 mg/kg on Day 1 of every 28-day cycle as a 30-60 min infusion.

    SPLIT: belantamab mafodotin will be administered in two equal divided doses, 2.5 mg/kg SPLIT dose of a 1.25 mg/kg dose on Day 1 and a 1.25 mg/kg dose on Day 8 of each 28-day cycle.

    STRETCH: belantamab mafodotin will be administered as 1.9 mg/kg dose on Day 1 of every alternate 28-day cycles (C1, C3, C5, C7 and so on.) Participants will also receive Lenalidomide 25 mg or 10 mg orally daily, on Days 1-21 of each 28 day cycle with Dexamethasone, 40 mg weekly per oral (PO)/intravenously (IV) on Days 1,8,15, & 22 of each cycle.

    Interventions:
    • Drug: Belantamab mafodotin
    • Drug: Lenalidomide
    • Drug: Dexamethasone
  • Experimental: Arm B: Belantamab mafodotin+bortezomib+dexamethasone
    Participants will receive SINGLE full dose of belantamab mafodotin as 3.4 mg/kg; 2.5 mg/kg; 1.9 mg/kg on Day 1 of each 21-day cycle. SPLIT: belantamab mafodotin will be administered in two equal divided doses: 3.4 mg/kg SPLIT as 1.7 mg/kg dose on Day 1 & 1.7 mg/kg dose on Day 8; 2.5 mg/kg SPLIT dosing as 1.25 mg/kg dose on Day 1 & 1.25 mg/kg dose on Day 8 of each 21-day cycle. STRETCH: belantamab mafodotin will be administered as single dose of 2.5 mg/kg on Day 1 of every alternate 21-day cycles (C1,C3,C5,C7 & so on), 1.9 mg/kg administered on Day 1 of every alternate 21-day cycles (C1,C3,C5,C7 and so on). Step Down(S/D) STRETCH=belantamab mafodotin 2.5 mg/kg dose will be administered on Day 1 C1 followed by 1.9 mg/kg starting dose on Day1 of alternate 21-day cycles C3 onwards (C3,C5,C7, & so on). Bortezomib will be administered at 1.3 mg/m^2 SC/IV on Days 1,4,8, & 11 of every 21-day cycle. Dex will be administered at 20 mg PO or IV on Days 1,2,4,5,8,9,11, & 12 of every 21-day cycle.
    Interventions:
    • Drug: Belantamab mafodotin
    • Drug: Dexamethasone
    • Drug: Bortezomib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 9, 2020)
152
Original Estimated Enrollment  ICMJE
 (submitted: May 23, 2018)
90
Estimated Study Completion Date  ICMJE August 26, 2022
Estimated Primary Completion Date April 28, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Capable of giving signed informed consent.
  • Male or female, 18 years or older (at the time consent is obtained).
  • Have confirmed diagnosis of Multiple Myeloma (MM) as defined by the IMWG.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 for Arm A and 0 to 2 for Arm B.
  • Have undergone stem cell transplant (SCT), or are considered transplant ineligible.
  • Have been previously treated with at least 1 prior line of MM therapy, and must have documented disease progression during or after their most recent therapy.
  • Must have at least ONE aspect of measurable disease, defined as one the following: Urine M-protein excretion >=200 milligram (mg)/24 hours, or; Serum M-protein concentration >=0.5 gram (g)/deciliter (dL) (>=5.0 g/Liter), or; Serum free light chain (FLC) assay: involved FLC level >=10 mg/dL (>=100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).
  • Participants with a history of autologous SCT, are eligible for study participation provided the following eligibility criteria are met: Autologous SCT was >100 days prior to study enrollment; No active bacterial, viral, or fungal infection(s) present; Participant meets the remainder of the eligibility criteria.
  • All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE], Version 4.03, 2010) must be Grade <= 1 at the time of enrollment, except for alopecia. Participants with Grade 2 neuropathy can be enrolled into Len/Dex treatment arm, but not into Bor/Dex treatment arm.
  • Adequate organ system functions as defined by the laboratory assessments.
  • The contraceptions used by female participants be consistent with local regulations, regarding methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of child bearing potential (WOCBP) or Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, during the intervention period and for at least 4 months after the last dose of belantamab mafodotin and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

WOCBP Participants Assigned to Arm A:

  • Due to lenalidomide being a thalidomide analogue with risk for embryo-fetal toxicity and prescribed under a pregnancy prevention/controlled distribution program, WOCBP participants will be eligible if they commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control (one method that is highly effective; beginning 4 weeks prior to initiating treatment with lenalidomide, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of lenalidomide treatment. Thereafter, WOCBP participants must use a contraceptive method that is highly effective (with a failure rate of <1% per year) for a further 3 months, and agree not to donate eggs (ova, oocytes) for the purpose of reproduction during this period: Two negative pregnancy tests must be obtained prior to initiating lenalidomide therapy. The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing lenalidomide therapy.

WOCBP Participants Assigned to Arm B

  • WOCBP assigned to Arm B must have a negative highly sensitive serum pregnancy test within 72 hours of dosing on C1D1 and agree to use effective contraception during the study and for 4 months after the last dose of belantamab mafodotin or 7 months from the last dose of bortezomib, whichever is longer.
  • Male participants using contraception should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Male participants are eligible to participate if they agree to the following:

Arm A: from the time of first dose of study until 6 months after the last dose of belantamab mafodotin 4 weeks after the last dose of lenalidomide, whichever is longer, to allow for clearance of any altered sperm.

Arm B: from the time of first dose of study until 6 months after the last dose of belantamab mafodotin or 4 months from the last dose of bortezomib (whichever is the longer) to allow for clearance of any altered sperm.

  • Male participants must agree to refrain from donating sperm and either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed below.
  • Agree to use a male condom even if they have undergone a successful vasectomy and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year when having sexual intercourse. Male participants should also use a condom with pregnant females. If the female partner of the male participant is pregnant at the time of enrollment, or becomes pregnant during the trial, the male participant must agree to remain abstinent (if it is consistent with their preferred and usual lifestyle) or use a male condom.

Exclusion Criteria:

  • Systemic anti-myeloma therapy (including systemic steroids) within <=14 days, or plasmapheresis within 7 days prior to the first dose of study drug.
  • Use of an investigational drug within 14 days or five half-lives (whichever is longer) preceding the first dose of study drug.
  • Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs.
  • Prior allogenic stem cell transplant. Note: Participants who have undergone syngeneic transplant will be allowed only if they have no history and no currently active, graft versus host disease (GvHD).
  • Evidence of active mucosal or internal bleeding.
  • Any major surgery within the last four weeks.
  • Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfill criteria.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease per investigator's assessment).
  • Participants with invasive malignancies other than multiple myeloma are excluded, unless the second malignancy has been considered medically stable for at least 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease. Note: Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction.
  • Evidence of cardiovascular risk including any of the following: Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block; History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening; Class III or IV heart failure as defined by the New York Heart Association functional classification system; Uncontrolled hypertension.
  • Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
  • Pregnant or lactating female.
  • Active infection requiring treatment.
  • Known Human immunodeficiency virus (HIV) infection.
  • Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb at Screening or within 3 months prior to first dose of study treatment).
  • Current corneal disease except for mild punctuate keratopathy.
  • Positive hepatitis C antibody test result or positive hepatitis C Ribonucleic acid (RNA) test result at Screening or within 3 months prior to first dose of study treatment.
  • Current corneal disease except for mild punctute keratopathy.
  • Participants Assigned to Treatment A (belantamab mafodotin plus Len/Dex): Participants unable to tolerate antithrombotic prophylaxis must be excluded; Discontinuation of prior treatment with lenalidomide due to intolerable AEs.
  • Participants Assigned to Treatment B (belantamab mafodotin plus Bor/Dex): Unacceptable AEs from previous bortezomib treatment; Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain from previous bortezomib treatment; Intolerance or contraindications to anti-viral prophylaxis.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com
Listed Location Countries  ICMJE Australia,   Canada,   France,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03544281
Other Study ID Numbers  ICMJE 207497
2017-004689-93 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided, after a research proposal is submitted and has submitted approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided, for an initial period of 12 months but an extension can be granted, when justified for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Iqvia Pty Ltd
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP